Method of making alpha-chlorobibenzyls, stilbenes and related compounds



United States atent This invention relates to a method of'rna'sing c p-substituted chloroethanes in which the substitutents may be substituted aikyl'chlorides that may be reacted in accord ance within the reaction set forth above are compounds such as 3-chloro-2-methylpropene; 3-chloro-2-ethyl propene; 3-chloro-2-propylpropene; l-methyl-Z-chloro-y methyletbene; 1-ethyl-Z-chloromethylethene; l-propyl-Z- chloromethylcthene; and the'like.

The organolitbium compounds that may be utilized to' react with the a-substituted allzyl chlorides in accordance selected from the group consisting of-aromatic, substituted aromatic, vinyl, substituted vinyl, and vinylidenyl and more particularly to the method of making c-chlo ro ,bibenzyls, stilbenes and related compounds. Y

The a,B-substi tuted chloroethanessuch as the cz-ChlOIO- bibenzyls and other related halides have been found to be useful for a variety of uses, such as pesticides, bacteriostats, and other biologically active compounds. These compounds have also found utility as intermediates, for

the manufacture of dyes, optical brightening agents, scintillators, etc. Although it has been possible to make some of these compounds prior to this invention, the method by which they were made often involved a series of long and complex steps which resulted in poor yields. Thus, the prior methods were quite unecono'mical as well as impractical.

Broadly stated, the present invention provides an exceedingly simple one-step method of making both aromatic and aliphatic a,fl-substituted chloroethanes. This method comprises the reacting of an int-substituted alkyl chloride, wherein the a-substituent is an aromatic or an (2,5 unsaturated group, with an organolithium compound, such as butyl lithium, in a solution of tetrahydrofuran at a low temperature.

By low temperature it is meant a temperature between about --100 C. and about 0 C.

The iii-substituted alkyl chlorides are reacted with the organolithium compounds in a solution of tetrahydrofuran as follows:

R-CHCl B"Ll R-CC'ILi no:

i i r p RCCIL1 R-onor RCC1CHI-R RI 7 R! R! wherein R is selected from the group consisting of aromatic, substituted aromatic, vinyl, substituted vinyl, or vinylidenyl groups and R is selected from the group consisting of hydrogen, and alkyl groups.

The iii-substituted alkyl chlorides utilized in this invention are those having the general formula R-cHo1 ii. I

wherein R is selected from the group consisting of aromatic, substituted aromatic, vinyl, substituted vinyl, or

vinylidenyl groups, and R is selected from the group c'onwith the method of this invention are the hydrocarbons of lithium g. lily represented by the formula erczn 1 R represents an aliryl hydrocarbon radical. Illustrat1vc organolithiurn compounds are butyllithium, ethyllithium, isobutyllithium, and the like.

lithium compound is butyllithium.

, The preferred solvent is tetrahydrofuran, however, other highly polar solvents may be equally operable.

The cc-ChlOl'Oblbfit'lZYlS made in accordance with the method of this invention may also be utilized as intermediates inthe formulation of stilbenes and the dehydrochlorinated substituted aliphatics, i.e., such as trienes and other olefinic compounds. The synthesis of stilbenes from a-chlorobibenzyls is accomplished by dehydrochlorination of the a-chlorobibenzyls in accordance with the equation below.

r c i 3 R! R! R! R! A R R R Stilbene 'In the equation above R and R are as hereinbefore defined for the a-substituted alkyl chlorides. As indicated, dehydrochlorination may be accomplished by gently heating the a-chlorobibenzyls until hydrogen chloride is evolved therefrom. Dehydrochlorination may also be readily accomplished by treatment of the u-chlorobibenzyl with strong bases, such as potassium tert. butoxide. 'The dehydrochlorination hi the olefinic chloroalkyl intermediates prepared by coupling the unsaturated alkyl chlorides is best accomplished by treatment with a strong base. Similarly, the olefinic chloroalkyl intermediates prepared by coupling the unsaturated alkyl chloride's' may also be dehydrochlorinated to produce the analogous olefiniccompounds For a better understanding of the details of the present invention, reference is directed to the following examples.

Examples of aromatic a-substituted alhyl chlorides that matic tit-substituted alkyl chlorides react to form the a,B- substituted alkyl chlorides. Examplesfoi the aliphatic EXAMPLE I (A) Synthesis of e-chlorobibenzyl 4.05 g. of benzyl chloride was added to 100 ml. of anhydrous tetrahydroturan. All equipment had been previously dried and flushed with argon and all reactions were run in an argon atmosphere. The reaction was cooled to C. with liquid nitrogen, and approximately 0.020 mole of butyllithiurn were slowly added in 40 ml. of hexane. The reaction was maintained at 90 C. for two hours. After two hours, the reaction mixture was poured into water to quench any active lithium compounds and the organic phase was separatedfrorng-the' aqueous phase. The aqueous phase was extracted with petroleum ether and the organic phases were combined. The organic phase was dried over sodium sulfate and stripped with vacuum. The residue of 4.04 grams was a faintly yellow liquid which analyzed 13.8% chloride by weight, which indicated a yield of 3.4 g. of

' C H CHClCH C H Y (B) Synthesis of trans-stilbenes 0.64 g. of this liquid was heated gently with a micro burner in a reflux system and gave off copious fumes of hydrogen chloride. 0n cooling the material solidified Patented Sept. 20, 1966 The preferred organoin an argon atmosphere.

to platelilte crystals, :1 chromatograph of this residue indicated 0.45 g. 'of trans-stilbene (M.P. 124 0.; calculated for C H i percent C., 93.4, (percent H, 6.67; found: C. 93.3, H. 6.68). The infrared and ultraviolet spectra of this material were identical to that of a control sample of u'ans-stilbene. culated as 2.72 g. or 94-95%.

EXAMPLE II (A) Synthesis of 1,2-di-(p-chlorophenyl) -1-chl0r0ethrme The overall yield of stilbenewas calas in previous examples. 8.4 g. of a clear, pale yellow liquid were obtained which on standing several hours,-

crystallized into white needles (M.P. 52-52.5 0.).

Calculated for C I-i cl: C, 78.5; H, 6.95; Cl, 14.5..

Found: C, 78.8; H, 7.05; Cl, 14.5. The infrared spectrum was consistent with the structure of 1,2-di-(p-methyl.

., phenyl)-l-chloroe-thane.

In the same manner as described in Example I, 6.42 g.

(40.1 moles) of p,u-dichlorotoluene was dissolved in 100 ml. of tetrahydrofuran. To this was added 21 mmoles of butyllithium in 14 ml. of hexane at -1 00 C. The reaction solution became pale blue-green which gradually faded. After 1 /2 hours, the reaction was poured into water. The organic phase was isolated and vacuum stripped. 5.4 g., 95% yield of a crystalline white solid was obtained. This solid was recrystallized from petroleum ether-tetrahydrofuran. The solid melted at 81-82 C. (Theoretically calculated for C I-1 C1 2 C, 58.8; H,

3.85; Cl,-37.3. Found: C, 59.4; H, 3.95; Cl, 36.0%.)

V (B) Synthesis of 4,4' -dimethylstilbene I i 1.09 g. of the product obtained in (A) was heated as described in earlier examples to effect dehydrochlorination. The solid residue was then recrystallized from tet-. rahydrofuran-petroleum ether to give a total of 0.80 g. of white platelets. (87% yield overall from p-metliyl- .benzyl chloride.) 1 (M.P., 186-186.5 C. uncorrected, lit.

. 180 C.; calculated for C l-I C, 92.3; H, 7.69. Found:

C, 92.0; H, 7.80.) The infrared spectrum was consistent with 4,4'-dlmethylstilbenc. l 0

EXAMPLE V V (A) Synthesis of LZ-di-(o-methylphenyl)-1-chl0roethane 10.2 g. (73 mmoles) of o-methylbenzyl chloride was dissolved in 100 ml. of anhydrous tetrahydrofuran under The infrared spectrum was consistent with 1,2-di-(p-chlo- I rophenyl) -1-chloroethane.

(B) Synthesis of 4,4'-dichl0r0stilbene 0.54 g. of the 1,2-di-(p-chlorophenyl)-1-chloroethane EXAMPLE 111 (A) Synthesis of 1,2-'di-(o-chlorophenyl)-1-chl0roethane 6.29 g. (39.3 mmoles) of o,a-dichlorotoluene was dissolved in 100 ml. of anhydrous tetrahydrofuran under an argon atmosphere. After cooling to 100 C., butyllithium (l9.7 mmoles) was added slowly in 14 m1. of anhydrous hexane. The solution became a pale rose in color. After 1% hours, the solution was pale orange. The solution was quenched in water and the product was isolated as in the previous examples. The product was a pale yellow liquid which contained 33.1% chlorine, or 91% 0f the theoretical amount of chlorine. From the infrared spectrum and the subsequent isolation of the 2,2- dichlorostilbene (Example 1V), it is apparent that this product is mainly -1,2-di(o-chloropheny1)-1-chloroethane.

(B) Synthesis of 2,2-dichlorostilbene C, 67.3; H, 4.02; Cl, 28.8.) The infrared spectrum was also consistent with the structure of 2,2'-dichlorostilbene.

EXAMPLEIV" (A) Synthesis of LZ-di-(p-methylphenyl)-I-chl0roethane 10.5 g. of a-chloro-p-xylene (4-methylbenzyl chloride) was dissolved in 100 ml. of anhydrous tetrahydrofuran The reaction was cooled to -100 C. and 37.3 mmoles of butyllithium in ml. of

' an argon atmosphere.

mmoles of butyllithium was added in 24 ml. of hexane. The solution turned pale yellow-orange. After three hours, the'reaction was quenched in water and the product isolated. 8.5 g. of a pale yellowish liquid was obtained which infrared analysis indicated it to be 1,2-di-(omethylphenyl)-1-chloroethane.

( B) Synthesis of 2,2'-dimethylstilbene =l.28 g. of the product of (A) was heated, as described in previous examples, and copious fumes of I-ICl were evolved. The solid residue was recrystallized from petroleum ether to give 0.60 g. (55% overall yield) of 2,2- dimethylstilbene crystals (M.P. after two recrystallizations, 78.5-80 C. uncorrected, calculated for C H C,

92.3; H, 7.69. Found: C, 92.3; H, 7.92). The infrared spectrum was 'consistent with the 2,2'-dimethylstilbene structure.

hexane was added slowly. The solution became pale orange, which gradually faded. After three hours, the I reaction was quenched in water andthe product isolated EXAMPLE VI Synthesis of 2,5-dimethyl-3-chl0rohexa-1,S-diene 5.88 g. of 2-methyl- 3-chloropropene (fi-methallylchloride) was dissolved in ml. of tetrahydrofuran under an argon atmosphere and the solution was cooled to 100 C. 33 mmoles of butyllithium in 22 ml. of hexane was added slowly. No color was formed. After two hours,

the reaction was quenched and the product isolated in the.

organic layer. The product was partially vacuum evaporated and then fractionally distilled to give 3.0 g. (-65 yield) of 2,3-dimethyl-3-chlorohexa-1,5-diene ('B.P. 52 C. at 17 mm. Hg, lit. 35 C. at 5 mm., n 1.4600, lit. 1.4612). The infrared spectrum was consistent with the compound underlined above.

While the invention has been-described with particular reference to a preferred embodiment thereof, it will be understood by those skilled in the art that variations from the specific method set forth above may be made without departing from the invention in its broadest aspects. I

We claim:

. '1. A method of making 0:,fi-Sllb5titt1t6d chloroethanes substituted phenyl wherein the substituents are selected from the group consisting of methyl, halogen, and methoxy, .vinyl and lower alkyl substituted vinyl groups and R is selected from the group consisting of hydrogen and alkyl, said method comprising the step of reacting an ta -substituted alkyl chloride of theformula B- fHCl After cooling to -100 C., 36.8

7 5 wherein R and R of'said a-substituted alkyl chloride is as defined for the a,fl-substituted chloroethanes,

with a lower alkyllithium compound in a solution of tetrahydrofuran at a temperature of betweenabout -100 C. and about 0 C.

2. The method of claim 1 wherein Ris phenyl and R I is hydrogen. 1

3. The method of 'claim 1 wherein R is para-chlorophenyl and'R is hydrogen.

4. The method of claim 1 wherein R is ortho-chlorophenyl and R is hydrogen.

5.. The method of claim 1 wherein R is para-methylphenyl R is-laydrosun.

6. The method of claim 1 wherein R is ortho-"neLhylphenyl and R is hydrogen. 1

7. The method of claim 1 wherein R- is isopropenyl and R is hydrogen. v

References Cited by the Examiner UNITED STATES PATENTS LEON ZTTVER, Primary Examiner.

15 K. H. JOHNSON, K. V. ROCKEY, Assistant Examiners. 

1. A METHOD OF MAKING A,B-SUBSTITUTED CHLOROETHANES OF THE FORMULA 